This proposal is to continue studies of the epidemiology, and genetic- environmental interaction in the etiology of non-insulin-dependent diabetes mellitus (NIDDM), and the potential for primary prevention. The emergence of diabetes mellitus (DM) in Pacific and Indian Ocean islanders, and these and other ethnic minorities in the USA has been concomitant with rapid socio-economic and environmental changes. There are also marked differences in susceptibility to NIDDM between ethnic groups. We will utilize the opportunities presented in Pacific and Indian Ocean populations for cross-sectional and longitudinal epidemiological studies, and crosscultural comparisons in 6 ethnic groups - Polynesians, Micronesians, Melanesians, Asian Indians, Chinese and African-origin Creoles. We will continue to pursue our previously defined objectives as they involve longitudinal studies and further analyses of data already collected. Additional objectives have arisen from our recent progress in modifying risk factors for NIDDM and cardiovascular disease (CVD) in Mauritius and include the evaluation of intervention activities aimed at reducing the incidence of NIDDM and IGT. Our longitudinal studies will focus on the island communities of Nauru, Western Samoa and Mauritius. Specifically. the research will continue: 1. To define trends in the prevalence and incidence of impaired glucose tolerance (IGT) and NIDDM in Nauru, W Samoa and Mauritius, and other countries if opportunities arise. 2. To assess the behavioural and environmental determinants and natural history of IGT and NIDDM in these populations, including the roles of hyperinsulinemia, overall obesity, fat distribution, physical activity, and diet 3. To investigate whether specific genetic markers exist in subjects with, or at risk of NIDDM, so high risk individuals might be targeted for prevention, and to assess whether any such factors operate similarly across ethnic groups. 4. To evaluate programs involving strategies for weight reduction, dietary modification and exercise for the primary prevention of IGT and NIDDM, and the modification of other CVD risk factor levels. 5. To define the prevalence, incidence and determinants of the micro- and macrovascular complications of NIDDM, their associated morbidity and mortality, and to investigate ethnic differences in risk. 6. To determine whether IGT and NIDDM are part of a non-communicable disease (NCD) cluster. 7. To pursue questions regarding the current classification and diagnostic criteria for DM. The proposed research is of great importance for the USA as NIDDM may be preventable. Thus, the elucidation of methods to detect "at risk" individuals, and a greater understanding of environmental precipitating factors would provide important directions for the development of primary prevention programs not only for NIDDM, but also other NCD, in the USA and other countries.